1124VOLUME23|NUMBER10|OCTOBER2017NATUREMEDICINETissuessuchastheintestinalepitheliumandthehematopoieticsystemcontinuouslyself-renewthroughtheactivityofadedicatedpopulationoftissue-specificstemcells,alsoknownasadultstemcells1,2.Unlikethebulkofthecellsthatpopulatethesetissues,adultstemcellsarelong-livedandgeneratecellularprogenythroughoutlifetoregeneratethemultiplespecialized,short-livedcellsthatultimatelyperformtissue-specificfunctions.TheCSCtheorystatesthattumorgrowthissimilarlyfueledbysmallnumbersoftumorstemcellshiddenincancers.Itexplainsclinicalobser-vations,suchasthealmostinevitablerecurrenceoftumorsafterinitiallysuccessfulchemotherapyand/orradiationtherapy,thephenomenonoftumordormancy,andmetastasis.ThefirstdecadeofthiscenturyhasseenanavalancheofreportsontheidentificationofCSCsinmanycommoncancertypes,includingleukemia3–5,breastcancer6,colorectalcancer7–9,andbraincancer10.TheCSCconcepthasinspiredthedesignofinnovativetreatmentstrategiesforthesecancers,notaimedatshrink-ingtumorbulk,butratheratexterminatingCSCs,thecellpopulationthatsustainslong-termgrowth.TheaimofthisreviewistodiscussrecentdevelopmentsintheCSCfieldwhilebearinginmindnewlyemergingviewsonthebiologyofnormalstemcells.Overthepastfewyears,experimentsinvolvinglineagetracingandcellablationinintacttumorshaveconfirmedthatmanyofthesetumorsharborstemcellsindedicatedniches11–16.Yet,ithasgradu-allybecomeclearthatCSCs(similarlytonormalstemcells)donotnec-essarilyhavetoberareand/orquiescent;multipleexamplesnowshowthattheycanbeabundantandcanproliferatevigorously.Furthermore,itisemergingthatstemcellhierarchiesmaybemuchmoreplasticthanpreviouslyappreciated17,aphenomenonthatcomplicatestheidenti-ficationanderadicationofCSCs.ThisreviewwillalsofocusonmajoradvancesinthedevelopmentofCSC-basedtherapies,someofwhicharecurrentlybeingimplementedintheclinicalsetting.TheshapingoftheCSCconceptWehavegivenanextensivehistoryoftheCSCfieldpreviously18.Herewebrieflyhighlightthemajorinfluenceofhematopoieticstemcell(HSC)researchinshapingt...
